tbuckley/cabot-search huggingface dataset:
Abstract 9465: A New Score for Predicting Results After Catheter Ablation for Atrial Fibrillation
Authors: Nastasa Alexandrina, Luminita Nirlu, Corneliu Iorgulescu, Dan-andrei Radu, Stefan Bogdan, Cosmin Cojocaru, Mohamed Dardari, Radu G Vatasescu
Journal: Circulation (2022)

Introduction: Cateter ablation (CA) for atrial fibrillation (AF) has been proven to be extremely effective in maintaining sinus rhythm but success rates still vary widely. Procedural costs are not negligible and a low, but nonetheless present, rate of potentially severe complications exists, therefore an accurate estimation of results is necessary in order to assess the risk-benefit ratio. Several studies have proposed different scores for predicting post-procedural success, such as APPLE, CAAP-AF, MB-LATER, SUCCESS, but most have not been validated yet in external cohorts, hence further research for the optimal formula is justified. Hypothesis: Our objective was to find independent predictors of recurrence after CA for AF and group them into a new, easy to calculate composite score. Methods: A total of 263 consecutive patients with AF who underwent CA in our centre were retrospectively analyzed. Variables that were significantly associated with recurrence risk according to univariate analysis were introduced in a Cox multivariate regression. The independent predictors of recurrence were used to create a new predicting score, after empirically assigning them different weights. Results: The mean follow-up period was 37.6 ± 23.4 months. The type of AF (persistent), f-waves &lt; 0.1mV, indexed LA volume, the presence of type II diabetes and smaller height were found to be independent predictors of recurrence and were used to create the new scoring model, VAT-DHF. The ROC curve for this new score showed an AUC 0.869, p&lt;0.0001, 95%CI [0.802-0.936] while those for APPLE and CHA 2 DS 2 Vasc showed AUC 0.765, 95% CI [0,637-0.893] and respectively, AUC 0.655,95%CI [0,580-0.730]. Patients who had a VAT-DHF score between 0-3.25 had a rate of success of 95.7%, those with a score between 3.25-6 of 76.3%, and those with a score ≥6 had a rate of success of 25% (p &lt;0.0001). A cut-off value of 5,75 gives the score a sensitivity of 87% and a specificity of 75%. Conclusions: The novel and simple VAT-DHF score is superior to the APPLE and CHA2 DS2 -VASc scores in predicting outcomes after catheter ablation for AF. It may provide a useful clinical tool to identify patients with low, intermediate or high risk of AF recurrence, but further validation is necessary.
Abstract 9397: Sex-Based Differences in Outcomes After Mitral Valve Repair for Severe Secondary Mitral Regurgitation
Authors: Francesco Nappi, Arnaldo Di magli, Antonio Nenna, Benedetto Umberto, Massimo Chello
Journal: Circulation (2022)

Background: Sex-based differences in outcomes after mitral valve repair for severe secondary ischemic mitral regurgitation (SIMR) is poorly understood. We examined differences in outcomes between men and women after mitral valve repair for severe SIMR. Methods: 96 patients with SIMR were randomized to undergo either papillary muscle approximation (PMA) with restrictive mitral annuloplasty (RMA) or RMA alone to evaluate efficacy and safety. The primary endpoint was death and major adverse cardiac or cerebrovascular events (MACCE) at 5 years. Results: 38 of the 96 enrolled (39.5%) were women. Five-year survival was 68% in women and 78% men (HR 1.48; 95% CI 0.67-3.24). Men and women had similar mortality rates in the PMA (HR 2.64; 95% CI 0.77-9.04) and RMA group (HR 0.93; 95%CI 0.31-2.78). Freedom from MACCE at 5 years was lower among women than men (6% vs 23%; HR 1.89; 95%CI 1.20-2.98). The hazard for MACCE was higher in women in the PMA group alone (HR 3.00; 95% CI 1.50-6.02). Freedom from treatment failure was similar between sexes (55% in women and 69% in men; HR 1.58; 95% CI 0.81-3.06). Similar functional status (26.3% vs 24.1%) and rehospitalization rates (23.7% vs 24.1%) were noted at 5 years. There were no significant differences in the percentage of change over 5 years in LVESD and LVEDD between the sexes. Conclusion: Women with SIMR who underwent mitral valve repair displayed no significant differences in the degree of five-year survival. MACCEs however, recurred more frequently in women.
Abstract 9859: Randomized Comparison of Bare Metal Stents Plus Colchicine vs Drug Eluting Stents: Preliminary Analysis of the Orca Trial (Oral Colchicine in Argentina)
Authors: Alfredo Matias M Rodriguez-Granillo, Camila Correa Sadouet, Juan Mieres, Carlos fernandez-Pereira, Roberto Cristodulo, Hernan Pavlovsky, Valeria Curotto, Sandra Swieszkowski, JOSE MILEI, Alejandro Barbagelata, Adnan Kastrati, Alfredo E Rodriguez
Journal: Circulation (2022)

Background: The use of colchicine has been associated with reduction of adverse cardiac events in patients with coronary artery disease (CAD). The role of this drug after percutaneous coronary intervention (PCI) with bare metal stents (BMS) has not been evaluated against isolated PCI with drug eluting stents (DES). Aim: The study was designed to test an improved cost-effectiveness with BMS plus colchicine (group BMS+C) compared to DES alone (group DES), provided its noninferiority in terms of major adverse cardiac events (MACE) at 1 year. Methods: This is a prospective, multicenter, randomized controlled trial performed in 4 centers. The trial has been registered at clinicaltrials.gov (NCT04382443). Study protocol and informed consent have been approved by an Independent Ethical and Review Board Committee and were presented to Argentina National regulatory authorities for Health, Technology and Medications. Patients in the BMS+C group received 0.5mg oral doses twice a day of colchicine for 3 months. Outpatient visits were scheduled at 1, 3, 6 and 12 months as well as at 3 and 5 years. Primary endpoints were to compare cost-effectiveness and MACE defined as composite of death, myocardial infarction (MI), cerebrovascular accident and ischemia-driven target vessel revascularization. Results: During February 2020 to April 2022, 412 patients with clinically indicated PCI were randomized in the study. Because 2 patients with COVID 19 at the time of randomization were excluded, the final study population was composed of 410 patients (205 patients in each group). Baseline demographic and angiographic characteristics were well balanced diabetes 19.5% vs 21.4%, Acute Coronary Syndromes 78% vs 75%, ST elevation MI 23% vs 21% multiple vessel CAD 44% vs 46%, culprit left anterior descending artery 58% vs 57.8%, peripheral vascular disease 3.4% in BMS+C and DES groups respectively.2.9% of patients in BMS+C didn’t complete the treatment for side effects (diarrhea). Presently, patients were follow at mean of 381 days ( range 45 to 839),1 -year follow-up was completed in 61%. Conclusion: A 3-month treatment with colchicine after PCI with BMS was feasible and safe. Final 1-year clinical outcomes and cost-effectiveness results will be available at the time of presentation.
Abstract 9398: Associations Between Blood Pressure, Race/Ethnicity, and Incident Stroke Type: A Pooled Cohort Analysis of ARIC, CARDIA, CHS, MESA, FOS, NOMAS
Authors: Kimson Johnson, Hanyu Li, Min Zhang, Mellanie V Springer, Andrzej Galecki, Rachael Whitney, Rebecca F Gottesman, Rodney A Hayward, Stephen Sidney, Mitchell S Elkind, Ralph L Sacco, W T Longstreth, Susan R Heckbert, Yariv Gerber, Kevin J Sullivan, Deborah A Levine
Journal: Circulation (2022)

Introduction: Stroke risk varies by systolic blood pressure (SBP) and race/ethnicity. Whether the relationship between cumulative mean SBP and first-time incident stroke type differs by racial/ethnic group is unknown. This study examines the relationship between cumulative mean SBP and first-time incident stroke among 3 major stroke types: ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and how race/ethnicity influences these relationships, using a pooled cohort analysis. Hypothesis: We hypothesize that race/ethnicity modifies the association between cumulative mean SBP and incident stroke type. Methods: Data were pooled from 38,325 participants with baseline age ≥18 and ≥1 SBP measurement before the first incident stroke from 6 US longitudinal cohorts from 1971 to 2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. A multivariable-adjusted Cox proportional hazard model was used to estimate the association between cumulative mean SBP, race/ethnicity, and time to incident stroke (overall, stroke type, and race/ethnicity*stroke type). Results: Median follow-up was 22.3 years. Mean (SD) baseline age was 53.2 (17.1) years, with 54.5% female, 24.9% Black, and 8.8% Hispanic. Baseline mean (SD) SBP was 136.8 (20.5) mmHg. Race/ethnicity modified the association of SBP with time to ICH (P-interaction=0.006) but no other stroke types. Compared to White participants, the association between higher SBP on ICH risk was greater in Black participants but not different in Hispanic participants (Table). A 10-mmHg higher SBP was associated with a higher risk of ICH than IS (Table). Conclusions: We found that race modifies the association between SBP and ICH risk, such that ICH risk is 19% higher per 10-mmHg for Black individuals than White individuals.
Abstract 9328: Sirt5 Deficiency Promotes Metabolic Reprogramming to Aggravate Cardiac Fibrosis
Authors: Maoxiong Wu, Haifeng Zhang, Woliang Yuan, Jing Tan, Zhaoqi Huang, Zhiteng Chen, Qi Guo, Zizhuo Su, Ying Yang, Qingyuan Gao, Qiong Qiu, Zhaoyu Liu, Jingfeng Wang, Yangxin Chen
Journal: Circulation (2022)

Introduction: Metabolic remodeling is critically involved in the pathogenesis of cardiac fibrosis. Glycolytic switch provides rapid energy production and biosynthetic intermediates to support proliferation and collagen synthesis of fibroblast. Sirtuin 5 (Sirt5) is a protein lysine de-succinylase that impacts diverse metabolic pathways. Objective: This study aimed to determine the function and mechanism of Sirt5 in cardiac fibroblast activation and cardiac fibrosis. Methods and Results: SIRT5 expression was examined in human and mouse myocardia, and was found to be downregulated in fibrotic myocardial tissues compared to non-fibrotic tissues. In a mouse model of myocardial infarction, Sirt5-knockout (KO) mice showed more severe cardiac fibrosis compared with wild-type mice. The aggravating cardiac fibrosis of Sirt5-KO mice were also found after transverse aortic constriction or angiotensin II plus phenylephrine-infusion. Proliferation and collagen synthesis of cardiac fibroblasts (CFBs) were both significantly enhanced by SIRT5 deficiency after AngII/PE-infusion in vivo and transform growth factor (TGF)-β1-treatment in vitro , but were attenuated by overexpression of Sirt5 in vitro . Moreover, Sirt5 deficiency enhanced a metabolic switch from oxidative phosphorylation to glycolysis in the isolated CFBs, and inhibition of glycolysis diminished the effect of Sirt5 deficiency on CFBs activation. Mechanistically, lysine succinylome analysis identified phosphoenolpyruvate carboxykinase 2 (Pck2), a rate-limiting enzyme in glycolysis pathway, as the protein mostly succinylated after Sirt5 deficiency. Activity of Pck2 was significantly inhibited by Sirt5 deficiency-mediated hypersuccinylation both in vivo and in vitro . K489R mutation of Pck2 diminished its succinylation and the reduction of its enzymatic activity mediated by Sirt5 deficiency, which also blunted the effect of Sirt5 deficiency on CFBs activation. Conclusions: Sirt5 deficiency enhances a metabolic reprogramming from oxidative phosphorylation to glycolysis in CFBs by succinylating Pck2, which promotes CFBs activation and aggravates cardiac fibrosis.
Abstract 9844: Particulate Matter 2.5, Metropolitan Status, and Heart Failure Outcomes in US Counties: A Nationwide Ecologic Analysis
Authors: Edward W Chen, Khansa Ahmad, SEBHAT ERQOU, Wen-Chih H Wu
Journal: Circulation (2022)

Epidemiological data on the relationship of particulate matter with a diameter of 2.5 micrometers or less (PM 2.5 ) with heart failure (HF) hospitalizations and mortality in the US are limited. Prior studies have focused on the effects of daily PM 2.5 exposure and HF hospitalizations in specific geographic locales in the US. Since PM 2.5 varies by geography, this study aimed to evaluate the relationship between annual ambient PM 2.5 concentration levels and HF hospitalizations and death at a county level across the US. We performed a cross-sectional analysis of county level HF hospitalizations, mortality, and ambient PM 2.5 concentration levels across 3135 US counties nationwide with adjustments for county-level demographics, socioeconomic factors, comorbidities, and healthcare-associated behaviors. County PM 2.5 showed a moderate correlation with HF hospitalization among Medicare beneficiaries (r=0.41) and a weak correlation with the overall county HF mortality (r=0.08) (p-values &lt; 0.01). There was an increase of 0.51 HF Hospitalizations/1,000 Medicare Beneficiaries and 0.74 HF deaths/100,000 residents for every 1 ug/m 3 increase in annual PM 2.5 concentration after adjustment for various county level covariates. The relationship between PM 2.5 concentration levels and both HF hospitalization and mortality remained significant after adjustment for county covariates. Additionally, the association between PM 2.5 and HF hospitalizations was comparable by metropolitan status of the counties. In conclusion, ambient PM 2.5 concentration level was associated with higher incidence of HF hospitalizations and deaths at the county level across the 3100 US counties. Future studies to examine policies aimed at reducing ambient particulate matter pollution and downstream effect of improving HF outcomes are warranted.
Abstract 9374: Machine Learning on Automated Measurement of 12 Leads Electrocardiography Can Predict Appropriate Shock in Patients With Implantable Cardioverter Defibrillator
Authors: Masato Shimizu, Ami Isshiki, Tateishi Ryo, Takahiro Tsunoda, Hiroko Miyazaki, Yoshiki Misu, Masao Yamaguchi, Yosuke Yamakami, Nobutaka Kato, Hiroshi Shimada, Shigeki Kimura, Hiroyuki Fujii, Makoto Suzuki, Mitsuhiro Nishizaki, Tetsuo Sasano
Journal: Circulation (2022)

Introduction: Prediction for appropriate shock in patients with implantable cardioverter defibrillator (ICD) is still challenging. We tried to predict the shock by machine learning (ML) model on automated microvolt-level measurement of 12-leads electrocardiography (ECG). Hypothesis: ML on 12-leads ECG can predict appropriate ICD shock. Methods: Consecutive 177 patients (61.5±14.4years, 141males, organic heart disease: 121cases) with ICD were enrolled. ECG was measured by ECAPs12c system (Nihon-Koden) at ICD implantation. Shock was defined as appropriate ICD shock and anti-tachycardia overdrive pacing. Statistic significant predictors were extracted by univariate Cox regression analysis. Because of many correlation/confounding/multicollinearity among the predictors, multivariate Cox was not performed, and machine learning (ML) predictive model was utilized to compare the importance of the predictors. Results: Fifty-six patients were treated by appropriate shock during the observation period (median during implantation to shock: 1.85years). Thirteen significant predictors were extracted, and T-axis showed the smallest P value of univariate Cox (P=0.0007). Random Forest Classifier model demonstrated high accuracy (0.740) and T-axis showed the most important role to build the model. Receiver operating characteristics (ROC) curve analysis indicated the cut-off value as 105 degree, and Kapan-Meier curve analysis demonstrated T-axis ≥105 degree group showed worse prognosis than T-axis &gt;105 degree group. Conclusions: ML of microvolt-level measurement of 12-leads ECG potentially had high predictive value for appropriate shock of ICD, and T-axis played an essential role for the prediction.
Abstract 9700: Totum-070 Reduces Hypercholesterolemia in Western Diet Fed Mice and Increases Cholesterol Fecal Excretion
Authors: Cedric Langhi, Yolanda F Otero, Florian Le Joubioux, Bruno Guigas, Sébastien PELTIER, Pascal Sirvent
Journal: Circulation (2022)

Lowering blood cholesterol level reduces the incidence of cardiovascular diseases. Totum-070 (T070) is a polyphenol-rich active substance composed by the association of 5 plant extracts. We tested the effect of supplementation of T070 in dyslipidemic mice and characterized the mechanisms of action. C57Bl/6 mice were fed with either a normal diet (ND) or a western diet (WD) for 6 weeks. Mice fed WD were split in different groups (vehicle, T070 1g/kg and T070 3g/kg) depending on the treatment received daily by gavage (n=14 per group). Compared to WD-fed mice, the concentration of total cholesterol was decreased after 3 weeks of supplementation by -9% (p&lt;0.05) and -12.7% (p&lt;0.01) with 1 g/kg T070 and 3 g/kg T070, respectively. At the end of the study, total cholesterol was reduced by -7.3% (n.s) and -11% (p&lt;0.01) with 1 g/kg and 3 g/kg T070 compared to WD-fed mice. Mice receiving 1g/kg T070 exhibited similar body weight gain than mice from the WD group. On the contrary, WD-fed mice receiving 3 g/kg T070 had reduced body weight gain by 29.5% compared to WD-fed mice (p&lt;0.01). The supplementation of T070 reduced hepatic steatosis in a dose-dependent manner with a 17.4% drop at 1 g/kg T070 (p&lt;0.05) and a 40% reduction at 3g/kg T070 (p&lt;0.0001) compared to WD-fed mice. Hepatic and intestinal gene expression were altered by WD feeding compared to ND, while supplementation with T070 tended to restore normal levels of expression on several genes implicated in lipid and lipoprotein metabolism. Fecal neutral sterols were quantified in feces collected at the end of the study. Sterol quantity was increased by 16% in feces from the 3g/kg T070 group compared to the WD group. Furthermore, a significant 13% increase in feces production was observed in mice supplemented with T070 3 g/kg compared to the mice fed with WD alone (p&lt;0.01). Fresh feces were harvested of the mice and composition of microbiota was assessed by 16S rDNA sequencing. WD induced a decrease in richness (Chao) and diversity (Shannon) indexes, compared to ND. T070 supplementation was able to partially restore diversity index, compared to WD. In conclusion, T070 supplementation is a promising strategy to prevent hypercholesterolemia though increased of fecal cholesterol excretion and amelioration of gut microbial imbalance.
Abstract 9822: Yield of a Familial Hypercholesterolemia Genetic Diagnosis After Electronic Health Record and Genomic Data Screening
Authors: Sam S Gidding, H Lester Kirchner, Andrew Brangan, WILLIAM HOWARD, Melissa A Kelly, Kelly Myers, Kelly Morgan, Timothy C Shuey, David Staszak, Natasha T Strande, Nicole Walters, Kristen D Yu, Katherine A Wilemon, Marc S Williams, Laney K Jones, Amy C Sturm
Journal: Circulation (2022)

Background: Data mining of electronic health records (EHR) has been used as a strategy to identify patients with undiagnosed familial hypercholesterolemia (FH). Most studies have been limited by the absence of both phenotypic and genotypic data in the same cohort. Methods: Using a subset of the Geisinger MyCode Community Health Initiative (MyCode) cohort with both exome sequencing and EHR data (n=130,257), we ran two FH screening algorithms to determine genetic and phenotypic diagnostic yields: the Mayo Clinic algorithm (Mayo), which identifies those with LDL-C levels &gt; 190 mg/dL, and FIND FH®, the Family Heart Foundation’s machine learning model, to identify individuals with phenotypes suggestive of FH. With 29,243 excluded by Mayo (for secondary causes of hypercholesterolemia, no lipid value in EHR), 52,034 excluded by FIND-FH (insufficient data to run the model), and 187 excluded for prior FH diagnosis, a final cohort of 59,729 participants screened by both algorithms was created. Genetic diagnosis was based on the presence of a pathogenic or likely pathogenic (P/LP) variant in 3 genes implicated in FH via genomic screening. Charts from 180 variant negative participants (60 controls; 120 identified by FIND FH and/or Mayo) were reviewed to calculate Dutch Lipid Clinic Network scores; a score &gt; 5 defined probable or definite FH. Results: Mayo flagged 10,415 subjects; 164 (1.6%) had an FH P/LP variant. FIND-FH flagged 573; 28 (4.9%) had an FH P/LP variant giving a net yield from both algorithms of 167/240 (70%). Confirmation of a phenotypic diagnosis was constrained by lack of EHR data on physical findings or family history (high cholesterol, premature atherosclerotic disease) required for score calculation. Phenotypic FH by chart review was present by Mayo and/or FIND-FH in 13/120 vs 2/60 not flagged by either (p&lt; 0.09). Conclusion: After excluding those with a prior FH diagnosis, applying two recognized phenotypic FH screening algorithms to the eligible MyCode cohort identified 70% of those with a P/LP FH variant. Limitations to this approach include participant exclusions for each algorithm, a low yield of positive genomic screening for Mayo, and a low yield of participants for FIND FH. Phenotypic diagnosis was rarely achievable due to missing data.
Abstract 9500: Patients’ Perspectives Regarding Generator Exchanges of Implantable Cardioverter-Defibrillators
Authors: Birju Rao, Sarah C Montembeau, Candace Speight, Dan D Matlock, Faisal M Merchant, Daniel B Kramer, Michal Horny, Neal W Dickert
Journal: Circulation (2022)

Background: Shared decision-making (SDM) is mandated for patients receiving primary prevention implantable cardioverter-defibrillators (ICD). Less attention has been paid to ICD generator exchange (GE) decisions. At the time of GE, patients’ risk of sudden cardiac death (SCD), risk of procedural complications, quality of life, or prognosis may have changed. This study was designed to explore how patients view GE decisions. Methods: In-depth interviews about perspectives regarding GE decisions were conducted with patients who had primary prevention ICDs implanted at Emory Healthcare from 2013-2021. Patients were also presented a hypothetical scenario where their ICD battery was depleted but their risk of SCD over 5 years at the time of battery depletion varied (10%, 5%, 1%). Patients were asked about their willingness to undergo GE under each of these conditions. Transcribed interview text was qualitatively coded using a multilevel template analytic method. Results: Fifty patients were interviewed, of whom 19 had a prior GE, 16 had no prior ICD therapies and 14 had improved left ventricular ejection fraction. Overall, even with low SCD risk, patients’ willingness to undergo a GE remained high (Figure). If their doctor recommended deferring GE, 15/49 patients still would not defer a GE. Many patients reported not relying on risk/benefit estimates to make GE decisions. Most also reported deferring the decision to their doctor, and many exhibited significant therapeutic inertia. One patient stated, “since I’m already wired for it⋯wouldn’t make sense to disregard it.” Conclusion: Strong default preferences push patients towards a GE. Risk stratifying patients for SCD at the time of GE may facilitate SDM and may reduce GE in very low-risk patients. However, even at 1% risk of SCD, which would not meet thresholds for ICD therapy, most patients would choose GE. This highlights provision of risk information alone seems unlikely to drive substantially different GE decisions.